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      Non-typhoidal Salmonella infections among children in a tertiary hospital in Ningbo, Zhejiang, China, 2012–2019

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          Abstract

          Background

          Non-typhoidal Salmonella (NTS), a common cause of diarrheal enterocolitis, may also cause severe invasive diseases. Limited information on NTS infections in children is available in China.

          Methods

          We performed a retrospective study of children admitted to the Ningbo Women and Children’s Hospital with culture-confirmed NTS infections between January 2012 and December 2019. Clinical and microbiological information were collected. We compared demographic, clinical and antibiotic resistance variables of invasive NTS (iNTS) infections and non-invasive NTS (non-iNTS) infections, and explored associations between hospitalizations for pediatric NTS infections and temperature and rainfall.

          Results

          A total of 166 pediatric hospitalizations due to NTS infection were identified during the 8-year study period. Most of the 166 children were <5 years old (93.4%). The primary serotype was Salmonella Typhimurium (62.6%). Of 166 children with NTS infections, 11 had invasive infection. Compared to 155 children with non-iNTS infections, we found that iNTS infections were more likely to occur in infants ≤6 months or children with an underlying medical condition of leukemia at admission, but iNTS infections less often presented with a symptom of diarrhea ( P <0.05 in all cases). The resistance rates of non-iNTS isolates to ceftazidime, ceftriaxone, cefepime, and aztreonam were significantly higher than those of iNTS isolates ( P <0.05 in all cases). In addition, compared with iNTS isolates, non-iNTS isolates were significantly associated with resistance to ≥4 CLSI (Clinical and Laboratory Standard Institute) classes ( P = 0.041, OR: 0.089, 95% CI: 0.009–0.901) and ≥2 first-line treatment agents ( P = 0.040, OR: 0.159, 95% CI: 0.028–0.916). On the other hand, we found that seasonal NTS hospitalizations were positively associated with average seasonal temperature (r = 0.961, P = 0.039) and average monthly rainfall (r = 0.921, P <0.001).

          Conclusion

          Non-iNTS accounts for the majority of infections in this study; infants ≤6 months and children with underlying medical conditions of leukemia are more likely to have invasive infection. The rates of antibiotic resistance in the iNTS isolates are generally lower than those in the non-iNTS isolates. On the other hand, high temperatures and heavy rainfall are positively associated with NTS hospitalizations among children in Ningbo.

          Author summary

          Non-typhoidal Salmonella (NTS) infection is a foodborne disease with a global heavy burden. NTS usually causes diarrheal enterocolitis in humans and may also cause severe invasive NTS (iNTS) infections. Antimicrobial agents are not recommended for non-severe NTS diarrhea, but they are recommended for people at risk of severe or invasive infection. However, the recognition of iNTS infection among children is difficult before culture. We studied children who had NTS infections in a tertiary pediatric hospital in Ningbo and found that iNTS infections were more likely to occur in infants ≤6 months or children with an underlying medical condition of leukemia at admission, while diarrhea was more common in children with non-iNTS infections. The high rates of antibiotic resistance among children with NTS in Ningbo calls for continuous NTS surveillance. On the other hand, high temperatures and heavy rainfall were positively associated with NTS hospitalizations among children. These findings may help us to improve measures for the prevention, diagnosis and treatment of NTS infections among children.

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          Most cited references58

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          Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

          Summary Background How long one lives, how many years of life are spent in good and poor health, and how the population’s state of health and leading causes of disability change over time all have implications for policy, planning, and provision of services. We comparatively assessed the patterns and trends of healthy life expectancy (HALE), which quantifies the number of years of life expected to be lived in good health, and the complementary measure of disability-adjusted life-years (DALYs), a composite measure of disease burden capturing both premature mortality and prevalence and severity of ill health, for 359 diseases and injuries for 195 countries and territories over the past 28 years. Methods We used data for age-specific mortality rates, years of life lost (YLLs) due to premature mortality, and years lived with disability (YLDs) from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to calculate HALE and DALYs from 1990 to 2017. We calculated HALE using age-specific mortality rates and YLDs per capita for each location, age, sex, and year. We calculated DALYs for 359 causes as the sum of YLLs and YLDs. We assessed how observed HALE and DALYs differed by country and sex from expected trends based on Socio-demographic Index (SDI). We also analysed HALE by decomposing years of life gained into years spent in good health and in poor health, between 1990 and 2017, and extra years lived by females compared with males. Findings Globally, from 1990 to 2017, life expectancy at birth increased by 7·4 years (95% uncertainty interval 7·1–7·8), from 65·6 years (65·3–65·8) in 1990 to 73·0 years (72·7–73·3) in 2017. The increase in years of life varied from 5·1 years (5·0–5·3) in high SDI countries to 12·0 years (11·3–12·8) in low SDI countries. Of the additional years of life expected at birth, 26·3% (20·1–33·1) were expected to be spent in poor health in high SDI countries compared with 11·7% (8·8–15·1) in low-middle SDI countries. HALE at birth increased by 6·3 years (5·9–6·7), from 57·0 years (54·6–59·1) in 1990 to 63·3 years (60·5–65·7) in 2017. The increase varied from 3·8 years (3·4–4·1) in high SDI countries to 10·5 years (9·8–11·2) in low SDI countries. Even larger variations in HALE than these were observed between countries, ranging from 1·0 year (0·4–1·7) in Saint Vincent and the Grenadines (62·4 years [59·9–64·7] in 1990 to 63·5 years [60·9–65·8] in 2017) to 23·7 years (21·9–25·6) in Eritrea (30·7 years [28·9–32·2] in 1990 to 54·4 years [51·5–57·1] in 2017). In most countries, the increase in HALE was smaller than the increase in overall life expectancy, indicating more years lived in poor health. In 180 of 195 countries and territories, females were expected to live longer than males in 2017, with extra years lived varying from 1·4 years (0·6–2·3) in Algeria to 11·9 years (10·9–12·9) in Ukraine. Of the extra years gained, the proportion spent in poor health varied largely across countries, with less than 20% of additional years spent in poor health in Bosnia and Herzegovina, Burundi, and Slovakia, whereas in Bahrain all the extra years were spent in poor health. In 2017, the highest estimate of HALE at birth was in Singapore for both females (75·8 years [72·4–78·7]) and males (72·6 years [69·8–75·0]) and the lowest estimates were in Central African Republic (47·0 years [43·7–50·2] for females and 42·8 years [40·1–45·6] for males). Globally, in 2017, the five leading causes of DALYs were neonatal disorders, ischaemic heart disease, stroke, lower respiratory infections, and chronic obstructive pulmonary disease. Between 1990 and 2017, age-standardised DALY rates decreased by 41·3% (38·8–43·5) for communicable diseases and by 49·8% (47·9–51·6) for neonatal disorders. For non-communicable diseases, global DALYs increased by 40·1% (36·8–43·0), although age-standardised DALY rates decreased by 18·1% (16·0–20·2). Interpretation With increasing life expectancy in most countries, the question of whether the additional years of life gained are spent in good health or poor health has been increasingly relevant because of the potential policy implications, such as health-care provisions and extending retirement ages. In some locations, a large proportion of those additional years are spent in poor health. Large inequalities in HALE and disease burden exist across countries in different SDI quintiles and between sexes. The burden of disabling conditions has serious implications for health system planning and health-related expenditures. Despite the progress made in reducing the burden of communicable diseases and neonatal disorders in low SDI countries, the speed of this progress could be increased by scaling up proven interventions. The global trends among non-communicable diseases indicate that more effort is needed to maximise HALE, such as risk prevention and attention to upstream determinants of health. Funding Bill & Melinda Gates Foundation.
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            The global burden of nontyphoidal Salmonella gastroenteritis.

            To estimate the global burden of nontyphoidal Salmonella gastroenteritis, we synthesized existing data from laboratory-based surveillance and special studies, with a hierarchical preference to (1) prospective population-based studies, (2) "multiplier studies," (3) disease notifications, (4) returning traveler data, and (5) extrapolation. We applied incidence estimates to population projections for the 21 Global Burden of Disease regions to calculate regional numbers of cases, which were summed to provide a global number of cases. Uncertainty calculations were performed using Monte Carlo simulation. We estimated that 93.8 million cases (5th to 95th percentile, 61.8-131.6 million) of gastroenteritis due to Salmonella species occur globally each year, with 155,000 deaths (5th to 95th percentile, 39,000-303,000 deaths). Of these, we estimated 80.3 million cases were foodborne. Salmonella infection represents a considerable burden in both developing and developed countries. Efforts to reduce transmission of salmonellae by food and other routes must be implemented on a global scale.
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              Salmonella enterica serovar Typhimurium skills to succeed in the host: virulence and regulation.

              Salmonella enterica serovar Typhimurium is a primary enteric pathogen infecting both humans and animals. Infection begins with the ingestion of contaminated food or water so that salmonellae reach the intestinal epithelium and trigger gastrointestinal disease. In some patients the infection spreads upon invasion of the intestinal epithelium, internalization within phagocytes, and subsequent dissemination. In that case, antimicrobial therapy, based on fluoroquinolones and expanded-spectrum cephalosporins as the current drugs of choice, is indicated. To accomplish the pathogenic process, the Salmonella chromosome comprises several virulence mechanisms. The most important virulence genes are those located within the so-called Salmonella pathogenicity islands (SPIs). Thus far, five SPIs have been reported to have a major contribution to pathogenesis. Nonetheless, further virulence traits, such as the pSLT virulence plasmid, adhesins, flagella, and biofilm-related proteins, also contribute to success within the host. Several regulatory mechanisms which synchronize all these elements in order to guarantee bacterial survival have been described. These mechanisms govern the transitions from the different pathogenic stages and drive the pathogen to achieve maximal efficiency inside the host. This review focuses primarily on the virulence armamentarium of this pathogen and the extremely complicated regulatory network controlling its success.
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                Author and article information

                Contributors
                Role: MethodologyRole: Writing – original draft
                Role: Data curation
                Role: Data curationRole: Investigation
                Role: Data curationRole: Investigation
                Role: Methodology
                Role: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                5 October 2020
                October 2020
                : 14
                : 10
                : e0008732
                Affiliations
                [1 ] Department of Clinical Laboratory, Ningbo Women and Children’s Hospital, Ningbo, Zhejiang, China
                [2 ] Neonatal Intensive Care Unit, Ningbo Women and Children’s Hospital, Ningbo, Zhejiang, China
                [3 ] Department of Blood Transfusion, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China
                [4 ] Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China
                Pontificia Universidad Catolica de Chile, CHILE
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-0004-4583
                http://orcid.org/0000-0001-9681-0507
                http://orcid.org/0000-0003-3450-7259
                Article
                PNTD-D-20-00511
                10.1371/journal.pntd.0008732
                7561262
                33017418
                c2325d2b-4825-402f-86f7-d5a1caa8c9bf
                © 2020 Ke et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 29 March 2020
                : 18 August 2020
                Page count
                Figures: 4, Tables: 3, Pages: 18
                Funding
                The author(s) received no specific funding for this work.
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